Lumizyme is supplied as a sterile, nonpyrogenic, white to off-white lyophilized cake or powder that must be reconstituted for intravenous administration. Certain measures, outlined below, should be followed to ensure proper product storage and preparation for infusion.
Lumizyme is available only in 50 mg units, supplied in single-use, clear Type I glass 20 mL (cc) vials. The vial's closure consists of a siliconized butyl stopper and an aluminum seal with a plastic flip-off cap. Lumizyme does not contain any preservatives and should be stored and handled according to these guidelines:
Lumizyme should be reconstituted, diluted, and administered by a health care professional using aseptic technique. Do not use filter needles during preparation. Reconstitution devices may be used to prepare successive vials of Lumizyme without the need to enter and withdraw from numerous vials of sterile water. Such devices are available from Genzyme by contacting Medical Information at 800-745-4447, option 2.
Remove Lumizyme vials from refrigeration and allow them to reach room temperature (about 30 minutes) before starting reconstitution. Organize a clean work area and prepare the following supplies:
You may need additional supplies, depending on the IV infusion protocol of your facility or practice.
1. Remove the required number of Lumizyme vials from refrigeration and let them reach room temperature (about 30 minutes).
2. Remove the plastic protective caps from each vial, and then slowly inject 10.3 mL of sterile water for injection, USP, to the inside wall of each vial.
INDICATION
LUMIZYME® (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated for patients 8 years and older with late (non-infantile) onset Pompe disease (GAA deficiency) who do not have evidence of cardiac hypertrophy. The safety and efficacy of LUMIZYME have not been evaluated in controlled clinical trials in infantile-onset patients, or in late (non-infantile) onset patients less than 8 years of age.
IMPORTANT SAFETY INFORMATION
WARNING
Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during LUMIZYME infusions. Therefore, appropriate medical support should be readily available when LUMIZYME is administered.
Because of the potential risk of rapid disease progression in Pompe disease patients less than 8 years of age, LUMIZYME is available only through a restricted distribution program called the LUMIZYME ACE Program. Only prescribers and healthcare facilities enrolled in the program may prescribe, dispense, or administer LUMIZYME. LUMIZYME may be administered only to patients who are enrolled in and meet all the conditions of the LUMIZYME ACE Program. To enroll in the LUMIZYME ACE Program call 1-800-745-4447.
Anaphylaxis and Allergic Reactions: Anaphylaxis and severe allergic reactions have been observed in patients during and up to 3 hours after LUMIZYME infusion. Some of the reactions were life-threatening and included anaphylactic shock, respiratory arrest, apnea, dyspnea, bradycardia, tachycardia, and hypotension. Other accompanying reactions included chest discomfort/pain, throat tightness, bronchospasm, wheezing, tachypnea, cyanosis, decreased oxygen saturation/hypoxia, convulsions, angioedema (including tongue or lip swelling, periorbital edema, and face edema), pruritus, rash, urticaria, hyperhidrosis, nausea, dizziness, hypertension, flushing/erythema, fever, pallor, peripheral coldness, feeling hot, restlessness, nervousness, headache, back pain, and paraesthesia. Some of these reactions were IgE-mediated.
If anaphylaxis or other severe allergic reactions occur, immediate discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with infusion interruption, administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. In some cases of anaphylaxis, epinephrine has been administered. Because of the potential for severe allergic reactions, appropriate medical support, including cardiopulmonary resuscitation equipment, should be readily available when LUMIZYME is administered. The risk and benefits of re-administering LUMIZYME following an anaphylactic or severe allergic reaction should be considered. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product.
Immune Mediated Reactions: Severe cutaneous reactions have been reported with alglucosidase alfa including necrotizing skin lesions. Systemic immune mediated reactions, including possible type III immune complex-mediated reactions have been observed with alglucosidase alfa. These reactions occurred several weeks to 3 years after initiation of alglucosidase alfa infusions. Skin biopsy in one patient demonstrated deposition of anti-rhGAA antibodies in the lesion. Another patient developed severe inflammatory arthropathy in association with fever and elevated erythrocyte sedimentation rate. Patients should be monitored for the development of systemic immune complex-mediated reactions involving skin and other organs while receiving LUMIZYME. If immune mediated reactions occur, discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment initiated. The risks and benefits of re-administering alglucosidase alfa following an immune mediated reaction should be considered. Some patients have successfully been rechallenged and have continued to receive alglucosidase alfa under close clinical supervision.
LUMIZYME ACE Program®: LUMIZYME is available only under a restricted distribution program called the LUMIZYME ACE (Alglucosidase Alfa Control and Education) Program. The purpose of the program is to ensure that the known risks of anaphylaxis and severe allergic reactions and the potential risks of severe cutaneous and systemic immune complex-mediated reactions associated with the use of LUMIZYME are communicated to patients and prescribers. In addition, the program is designed to mitigate the potential risk of rapid disease progression in infantile-onset Pompe disease patients and late (non-infantile) onset Pompe disease patients less than 8 years of age for whom the safety and effectiveness of LUMIZYME have not been evaluated.
For information about the ACE Program call 1-800-745-4447.
Risk of Acute Cardiorespiratory Failure: Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Appropriate medical support and monitoring measures should be readily available during infusions and some patients may require prolonged observation times.
Precautions for General/Regional Anesthesia: Administration of general anesthesia can be complicated by the presence of severe cardiac and skeletal (including respiratory) muscle weakness, therefore, caution should be used when administering general anesthesia in Pompe disease patients.
Monitoring: Laboratory Tests: Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter. Testing for IgG titers may also be considered if patients develop allergic or other immune mediated reactions. Patients who experience anaphylactic or allergic reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis.
Adverse Reactions:
Serious adverse reactions reported with LUMIZYME in the randomized, double-blind, placebo-controlled study included anaphylaxis. Anaphylactic reactions included: angioedema, throat tightness and chest pain/discomfort. One patient with a history of Wolff-Parkinson-White syndrome experienced a serious adverse reaction of supraventricular tachycardia. Other serious adverse events that occurred in a higher incidence in LUMIZYME treated patients compared to placebo included coronary artery disease, intervertebral disc protrusion, pneumonia, gastroenteritis, and dehydration.
The most common adverse reactions observed in clinical studies were infusion reactions. Infusion reactions that occurred in LUMIZYME treated patients at an incidence of ≥ 5% compared to placebo included anaphylaxis, urticaria, diarrhea, vomiting, dyspnea, pruritus, rash/erythema, pharyngolaryngeal pain, neck pain, hypoacusis, flushing/feeling hot, pain in extremity, fall and chest discomfort. Additional infusion reactions observed in other clinical trials and expanded access programs with LUMIZYME included respiratory distress, cough, livedo reticularis, agitation, irritability, retching, rigors, tremor and increased lacrimation. Infusion reactions may occur during or within 2 hours after completion of the infusion. Delayed onset infusion reactions defined as adverse reactions that occurred within 48 hours after completion of LUMIZYME infusion, occurred in LUMIZYME treated patients at an incidence of ≥3% compared to placebo treated patients in a controlled clinical trial. Patients should be counseled about the possibility of delayed onset infusion reactions and given proper follow up instructions.
If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of antihistamines and/or antipyretics may ameliorate the symptoms. If severe infusion or allergic reactions occur, immediate discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment should be initiated. Patients who have experienced infusion reactions should be treated with caution when they are re-administered LUMIZYME.
In postmarketing experience with LUMIZYME, deaths, and serious adverse reactions have been reported, including anaphylaxis. Adverse events resulting in death reported in the postmarketing setting with LUMIZYME treatment included cardiorespiratory arrest, respiratory failure, hemothorax, pneumothorax, cardiac failure, sepsis, aortic dissection, cerebrovascular accident, and skin necrosis. The most frequently reported serious adverse reactions were infusion reactions. The following serious adverse events have been reported in at least 2 patients: dyspnea, respiratory failure, bronchospasm, stridor, decreased oxygen saturation/hypoxia, pharyngeal edema, chest discomfort, chest pain, hypotension, hypertension, erythema, flushing, lung infection, tachycardia, cyanosis, and hypersensitivity. One case of hyperparathyroidism has been reported.
Immunogenicity: In the randomized, double-blind, placebo-controlled study, all patients with available samples treated with LUMIZYME (N=59, 100%) developed IgG antibodies to alglucosidase alfa. All patients who developed IgG antibodies did so within the first 3 months of exposure (median time to seroconversion was 4 weeks). A small number of LUMIZYME treated patients in clinical trials and postmarketing setting who were evaluated tested positive for presence of alglucosidase alfa-specific IgE antibodies. Some of these patients experienced anaphylaxis. Some patients who tested positive for alglucosidase alfa-specific IgE antibodies were successfully rechallenged with LUMIZYME using a slower infusion rate at lower initial doses and have continued to receive treatment under close clinical supervision. Patients who develop IgE antibodies to alglucosidase alfa appear to be at a higher risk for the occurrence of anaphylaxis and severe allergic reactions. Therefore, these patients should be monitored more closely during administration of LUMIZYME.
To report suspected adverse reactions, contact Genzyme Medical Information at 800-745-4447, option 2.
Please see the full prescribing information for complete details, including boxed warning.